RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhanced antitumour response of gold nanostar-mediated photothermal therapy in combination with immunotherapy in a mouse model of colon carcinoma.
Enhanced antitumour response of gold nanostar-mediated photothermal therapy in combination with immunotherapy in a mouse model of colon carcinoma.
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本研究表明,PTT 联合 DC 免疫治疗和阿替利珠单抗可有效克服 CT26 肿瘤的不敏感性。这些发现凸显了该联合方案在结直肠癌治疗中的潜力。
本研究探讨了将PTT与基于树突状细胞(DC)的免疫疗法及抗PD-L1免疫检查点阻断(ICB)疗法联合应用于结直肠癌的潜力,并阐明了其潜在机制。
将CT26荷瘤小鼠分为七个治疗组:对照组、atezolizumab(A)组、树突状细胞(DC)组、pAuNSs介导的PTT(PTT)组、PTT联合atezolizumab(PTT + A)组、PTT联合树突状细胞(PTT + DC)组,以及PTT联合树突状细胞和atezolizumab(PTT + DC + A)组。监测治疗效果。
PTT上调了大多数免疫细胞膜受体基因,包括PD-L1,并下调了与抗原呈递和T细胞活化相关的基因。尽管PTT + A和PTT + DC治疗显示出部分肿瘤生长延缓,但PTT联合DCs和阿替利珠单抗(PTT + DC + A)表现出最显著的抗肿瘤效果,完全缓解率为50%,并延长了生存期。第14天,未响应小鼠的肿瘤样本显示T细胞募集不足是肿瘤未治愈的原因。值得注意的是,经PTT + DC和PTT + DC + A治疗治愈的小鼠未检测到肺结节。
This study investigated the potential of combining PTT with dendritic cell (DC)-based immunotherapy and anti-PD-L1 immune checkpoint blockade (ICB) therapy against colorectal cancer and elucidated the underlying mechanisms.
The CT26 tumour-bearing mice were divided into seven treatment groups: control, atezolizumab (A), dendritic cells (DC), pAuNSs-mediated PTT (PTT), PTT combined with atezolizumab (PTT + A), PTT combined with dendritic cells (PTT + DC), and PTT combined with dendritic cells and atezolizumab (PTT + DC + A). Therapeutic efficacy was monitored.
PTT upregulated most immune cell membrane receptor genes, including PD-L1, and downregulated genes associated with antigen presentation and T cell activation. Although the PTT + A and PTT + DC treatments showed partial tumour growth retardation, the combination of PTT with DCs and atezolizumab (PTT + DC + A) exhibited the most significant antitumour effect, with a complete remission rate of 50% and prolonged survival. On day 14, tumour samples from non-responsive mice revealed insufficient recruitment of T cells as the reason for uncured tumours. Notably, mice cured with PTT + DC and PTT + DC + A treatments showed no detectable lung nodules.
This study demonstrated that the combination of PTT with DC-based immunotherapy and atezolizumab effectively overcomes the non-sensitive nature of CT26 tumours. These findings highlight the potential of this combination approach for colorectal cancer treatment.
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